Second seed and 12-time Grand Slam winner Nadal began the week as the favourite to win the men's title at Flushing Meadows.
The 27-year-old Spaniard was unbeaten on hardcourts in 2013, having won 15 consecutive matches and picking up titles in Indian Wells, Montreal and Cincinnati.
Meanwhile, 21-year-old Harrison, who was ranked 97th in the ATP World Rankings, had failed to progress beyond the final-32 stages in his last three tournaments on this surface.
Would there be an upset, or would Nadal's sensational run continue? Find out how the match unfolded below with Sports Mole's blow-by-blow text updates.
7.51pmGood evening. One male seed has already fallen today. British number three Dan Evans, ranked 179th in the world, overcame 11th seed Kei Nishikori 6-4 6-4 6-2. That result was certainly a shock, but its place on the back pages would be in severe doubt if Nadal were to lose to Harrison.
7.52pmPREDICTION: I'm going to stick my neck on the line and say that WON'T happen. I fully expect Rafa to progress in straight sets.
7.55pmThese two players have only faced each other on one previous occasion. Earlier this year, they met at Indian Wells, where Nadal prevailed 7-6 6-2.
7.57pmNadal and Harrison have appeared inside a breezy Arthur Ashe Stadium. The match is due to begin in around six minutes.
Nadal 0-0* HarrisonBREAK POINT NADAL: Rafa has just hit the shot of the tournament so far... Deep behind the baseline and returning a Harrison overhead, he somehow manages to raise his racquet above his head and whip a forehand pass beyond the American, who is at the net.
Nadal 6-4 *2-1 HarrisonNADAL BREAKS: Nadal takes control of the second set in a flash, breaking to 15 with some unstoppable baseline hitting.
Nadal 6-4 *2-1 HarrisonIT'S SPITTING! Light drizzle begins to fall from the New York sky, prompting umpire Asderaki to temporarily suspend play. However, it looks like it is only a passing shower and the players are staying on court for now.
Nadal 6-4 *2-1 HarrisonThe rain has stopped, ball boys are drying the lines with towels and, to the delight of many in the crowd, Nadal is changing his shirt. Gun show.
Nadal 6-4 6-2 0-0* HarrisonAnyone for a New York bagel? I fancy that one could be on the menu in set three. Nadal is really firing now and, in truth, Harrison looks like he is feeling a bit sorry for himself.
Nadal 6-4 6-2 0-0* HarrisonBREAK POINT NADAL: Oh no! This is painful watching. Harrison loses his head and his service could soon follow. Four errors, three of them unforced, turn the game on its head and Nadal is now chomping at the bit, looking for his fourth break.
Nadal 6-4 6-2 *1-0 HarrisonNADAL BREAKS: Harrison pushes a cumbersome forehand long and Nadal claims an early break - just as he did in sets one and two.
Nadal 6-4 6-2 2-0* HarrisonSport is supposed to be fun, but Harrison looks like he could go all Sabine Lisicki and burst into tears at any moment. The crowd has also gone a bit flat. Rafa is playing very well, but this is not a contest.
Nadal 6-4 6-2 *3-0 HarrisonNADAL BREAKS: Harrison spurns two more game points and Rafa punishes him by breaking again courtesy of a stunning backhand pass.
Nadal 6-4 6-2 *3-0 HarrisonTWO BREAK POINTS FOR HARRISON: Shock! A combination of fearless, almost apathetic, ball striking from Harrison and a momentary period of slackness from Rafa provide the American with his first break points of the match. 15-40.
Nadal 6-4 6-2 4-0* HarrisonRafa reels off four straight points and holds to deuce. Perhaps the Spaniard was simply teasing his opponent?
Nadal 6-4 6-2 *4-1 HarrisonHARRISON HOLDS: The American, who failed to convert game points in games one, three and four in this third set, holds to 30 in game five and avoids the indignity of a bagel.